The recent economic downturn was caused by the private sector, especially big banks and investment companies. As an average citizen and public sector employee, I was happy to help out by giving the private sector bundles of taxpayer money in order to rescue them from their own greed. After all, that's what the public sector is for—to support free enterprise with government money.

Private companies need your help more than ever. They need corporate tax cuts. You can't expect them to support corporate welfare payments with high corporate tax rates. That would be like giving money to themselves and they don't teach that in business school, do they?

Sunday, January 30, 2011

I'm very uncomfortable with popular claims about the migration of modern humans into Asia and Europe. You often see the date as 50,000 years ago and most people seem to think that this was a sudden event associated with the destruction of ancient hominids (Neandertal, Homo erectus) who lived in Asia and Europe at this time.

The recent date was based largely on mitochondrial DNA sequences and it required a reliable time reference that just wasn't there. As other nuclear genes were analyzed the dates indicated much older migrations. Then there's the fossil evidence. I'm not able to judge that evidence but it didn't seem to me to be as neat and tidy as a sudden exodus at 50,000 years ago would require.

Fortunately we have John Hawks, a scientist who's area of expertise covers archeology AND population genetics. He thinks that the date for "Out of Africa" should be older and he can back up his skepticism with evidence. Read his latest posting at: Jebel Faya and early-stage reduction. Will the new date end up being 100,000 years ago—or maybe even 150,000 years ago?

Since John doesn't allow comments on his blog I thought I'd open up some discussion here. John, aside from the question of modern Homo sapiens, when did Neandertals leave Africa and when was the migration of Homo erectus? How secure are those dates?

P.S. As I was about to publish this post I did a quick check to see when the movie was released. It was 1985. This means that none of the students in my molecular evolution class were alive when it came out. I feel old.

Saturday, January 29, 2011

The battle between science and religion has been going on for centuries. Part of the conflict is over the teaching of evolution in American public schools. Religious parents don't want their children exposed to ungodly evolution and the most vocal of them want creationism taught as part of the science curriculum.

Now you might think that that this particular battle has been decisively won by the "good guys" because of all the court victories. Not so. The results in the classroom reveal that evolution is not being taught except in the most liberal states and a substantial number of teachers are teaching creationism in spite of the law.

I want to raise another question. What good has it done to win all the court cases? Has it prevented an even worse disaster? Has relying on lawyers to defend evolution been the right strategy or should more emphasis have been placed on promoting good science instead of the American Constitution?

There's one point that few people raise. Evolution is taught badly even in universities—and so is everything else. You might think that by the time a student graduates with a degree from university he or she will be knowledgeable enough to reject superstition and rely on critical thinking. If we can't even do a good job of teaching adults in university then how can we expect public school teachers to do any better? In an ideal world every parent who is a university graduate should be an ally of their child's teacher when it comes to supporting good science education.

PZ Myers gave a talk at the Atheist Alliance International meeting in Montreal last October. It was taped for TVOntario's "Big Ideas" show and it will air tomorrow (Sunday, January 30, 2011) at 5:30 pm.

Friday, January 28, 2011

I hope you all appreciate the fact that I've not been inundating you with photos and videos of my granddaughter, Zoë. You probably don't share my view that she's the third most wonderful girl in the world.

Anyway, just in case you were feeling neglected, here's Zoë taking her first steps. She was almost walking during her visit at Christmas but now she's really a toddler.

The delivery of organic matter to the primitive Earth via comets and meteorites has long been hypothesized to be an important source for prebiotic compounds such as amino acids or their chemical precursors that contributed to the development of prebiotic chemistry leading, on Earth, to the emergence of life. Photochemistry of inter/circumstellar ices around protostellar objects is a potential process leading to complex organic species, although difficult to establish from limited infrared observations only. Here we report the first abiotic cosmic ice simulation experiments that produce species with enantiomeric excesses (e.e.'s). Circularly polarized ultraviolet light (UV-CPL) from a synchrotron source induces asymmetric photochemistry on initially achiral inter/circumstellar ice analogs. Enantioselective multidimensional gas chromatography measurements show significant e.e.'s of up to 1.34% for (13C)-alanine, for which the signs and absolute values are related to the helicity and number of CPL photons per deposited molecule. This result, directly comparable with some L excesses measured in meteorites, supports a scenario in which exogenous delivery of organics displaying a slight L excess, produced in an extraterrestrial environment by an asymmetric astrophysical process, is at the origin of biomolecular asymmetry on Earth. As a consequence, a fraction of the meteoritic organic material consisting of non-racemic compounds may well have been formed outside the solar system. Finally, following this hypothesis, we support the idea that the protosolar nebula has indeed been formed in a region of massive star formation, regions where UV-CPL of the same helicity is actually observed over large spatial areas.

The authors assume that the primodial soup speculation about the origin of life is the most reasonable explanation. According to this widely believed scenario, life originated in a soup of organic molecules that supplied most of the molecules of metabolism such as glucose and amino acids (and nucleotides?). Presumably once life got underway these molecules were used up and only then did metabolic pathways evolve to synthesize these molecules.

The competing hypothesis is Metabolism First [Metabolism First and the Origin of Life]. In this scenario, the first steps involved the establishment of simple oxidation-reduction reactions across a "membrane" using inorganic molecules. Once this supply of energy was in place the first pathways led to synthesis of simple organic molecules like acetate and glycine.

What's wrong with the Primordial Soup model? Well, for one thing, it's awfully hard to imagine how incoming asteroids could supply enough material to make a difference. The maximum concentration of all amino acids in the ocean, for example, could never have been more than 10-100 pM and that's optimistic [Can watery asteroids explain why life is 'left-handed'?].1

Instead of trying to prove that asteroids could carry a slight excess of L-amino acids, I wish these workers would apply a bit of healthy skepticism to the subsequent steps of the scenario. It's not reasonable to assume that minute quantities of amino acids could ever fuel the origin of life. Incidentally, the Primordial Soup Hypothesis also imagines that early cells used exogenous glucose as a fuel. This implies that the glycolysis pathway is more primitive that the gluconeogenesis pathway for synthesis of glucose. Unfortunately the data disproves this prediction. Gluconeogenesis is more ancient and glycolysis evolved later [Aldolase in Gluconeogenesis & Glycolysis]. A nasty little fact.

The real problem is not that metabolism firstists such as Bill Martin are right and soupists are wrong—although that's a very real possibility. The problem is that most scientists are not thinking critically about the origin of life. There are several possibilities and none of them are particularly convincing. However, the Primordial Soup Hypothesis has a number of glaring weaknesses that need to be addressed honestly and it doesn't do anyone any good if scientists sweep these weaknesses under the rug.

1. We're talking about a primordial soup where the concentration of L-alanine might be 0.50 pM and the concentration of D-alanine might be 0.49 pM. That's supposed to be enough for life based on amino acids to evolve and to lead to the subsequent preference for synthesizing exclusively L-amino acids. How, exactly, does that work?

Wednesday, January 26, 2011

Here's Daniel Dennett speaking in Montreal last October. He addresses the "problem" of what should replace religion once we get rid of it. You may wonder what "problem" he's referring to. After all, when you visit countries in Europe you don't see a pressing need to come up with some institutions that replace religion.

Here's a list of good things that religion provides according to Dennett: hope, love, beauty, joy, and moral teamwork. These are the things we get from organized religion.

Really? I haven't noticed that these things are missing in the lives of my atheist friends. Nor have I noticed that the people of Denmark or Belgium are loveless, joyless and incapable of moral teamwork. What the heck is he talking about? What he's talking about is the idea that a church is "the place where if you have to go there they have to take you in."

... churches do that very well. They are a safety net of last resort for many people, and not just poor people, ... churches open their doors to these people and they can do a better job at this than government agencies.

He's talking about churches as safety nets and sources of social support. What he's talking about is the (possible) necessity of churches in a country that rejects socialism. He's talking about America but he doesn't admit it.

You can watch the faces of this mostly Canadian audience, as I did, to see how well Dennet's ideas are being received. There's a lot of puzzled looks as you might expect in a country where socialized medicine is a universal right. Why do you need churches for those things that any just society must provide? Why do you need churches when you have publicly funded community centers where you can hang out with your friends and neighbors?

Things go rapidly downhill from that point on (about 12 minutes into the talk). The next part of the talk is about religious music. It includes some truly excruciating atheist gospel songs that the audience is subjected to. (They cut out a large part of that from the video.) The remainder of the talk has very little to do with the necessity of religion.

Sunday, January 23, 2011

This video is making the rounds. I'm including it here because so many people have been discussing "civility" and "politeness" in the wake of the Tuscon mass killing. In my opinion, it's not lack of civility that's the problem. The problem arises when you start treating your opponents as anti-American and unpatriotic and their ideas as illegitimate (not just a difference of opinion). That's when it becomes reasonable to consider using force to prevent your enemy from destroying the country. You are protecting America against dictatorial traitors and that's exactly what reasonable citizens should do.

Glen Beck is a master of this technique. He should not be surprised if some of his followers jump to the obvious conclusion. Indeed, CUNY professor Frances Fox Piven (78 years old) has been receiving death threats ever since Beck's rant aired on television last November [Glenn Beck's Ranting Sparks Death Threats Against 78-Year-Old Sociologist]. Is anyone surprised?

Why does Glen Beck still have a job?

A note to Canadian readers. Pay attention. This is the real problem, not simple lack of politeness.

Friday, January 21, 2011

What did you learn at university? Not much, it seems, according to the data in a new book titled Academically Adrift. The book is reviewed in the latest issue if Inside Higher Ed [Academically Adrift].

The data aren't surprising. The authors of the book show that 36% of students failed to learn anything after four years of college. Of those who did learn something, the gains were very modest.

Why don't students learn?

The main culprit for lack of academic progress of students, according to the authors, is a lack of rigor. They review data from student surveys to show, for example, that 32 percent of students each semester do not take any courses with more than 40 pages of reading assigned a week, and that half don't take a single course in which they must write more than 20 pages over the course of a semester. Further, the authors note that students spend, on average, only about 12-14 hours a week studying, and that much of this time is studying in groups.

Who's to blame for this sorry state of affairs?

Debra Humphreys, vice president for communications and public affairs of AAC&U, said that she viewed the book as "devastating" in its critique of higher education. Faculty members and administrators (not to mention students and parents) should be alarmed by how little learning the authors found to be taking place, she said. Humphreys also said that the findings should give pause to those anxious to push students through and award more degrees -- without perhaps giving enough attention to what happens during a college education.

"In the race to completion, there is this assumption that a credit is a credit is a credit, and when you get to the magic number of credits, you will have learned what you need to learn," she said. What this book shows, Humphreys added, is that "you can accumulate an awful lot of credits and not learn anything."

None of this is news my colleagues and me. Problem is, there's not much we can do about it. If we increase the rigor of our biochemistry courses and start demanding more of our students then the result won't be increased learning. It will simply mean that undergraduates will avoid biochemistry courses. In fact, that's already happening since the University of Toronto has developed dozens of new programs that will award degrees in the biological sciences without ever forcing students to take a rigorous course.

This brings up a question that I often ask my students. If university is supposed to be difficult (rigorous) then it's likely that some students won't be capable of completing a degree. In an ideal setting with expertly taught, challenging, programs, what percentage of the incoming class of students should expect to complete a degree? Clearly the answer can't be 100% because that bar is way too low. Should it be 50% as it was in many universities in the past? Lower?

The graduation rate at the University of Toronto has been pretty constant over the past decade at 73-75%. I assume that many of the students who drop out do so for reasons other than the rigor of university courses (e.g., personal problems, financial problems, transfers, changing goals etc.). Let's assume that this accounts for 15% of the drop-outs.

This Friday night at 7:30 p.m. CFI Canada launches the much awaited Extraordinary Claims campaign with three lectures, a panel discussion and an audience question-and-answer session, for a critical analysis of Psychics, Homeopathy and Christ. The invitation has also been respectfully extended to hundreds in the Toronto area who support one or more of these claims. The night promises to be an exciting and fascinating experience. Don't miss out!

Professor James Alcock of York University will address Psychics, Dr. Iain Martel of the Committee for the Advancement of Scientific Skepticism (CASS) will analyze Homeopathy and John Loftus, a former Christian Minister and apologist, will take on Christ. The night will be moderated by Michael Kruse, co-chair of CASS.

Date and time: Friday, January 21, 7:30 p.m. to 10:00 p.m. CFI members have advance access to seating beginning at 6:45 p.m. Non-members will be seated shortly before the presentation begins.

Admission prices: $8 general, $5 students and FREE for CFI members. Become a CFI member or renew.

Prepaying admission by PayPal is offered HERE. Please print out your PayPal receipt and bring it with you.

CFI members please bring your membership card and check the expiration date to ensure you can get in for FREE. If you are unsure then call Centre for Inquiry Ontario at (416) 971-5676 or e-mail info@cficanada.ca

A members-only reception is being held at 5:30 p.m. at CFI Ontario (216 Beverly St.).

Thursday, January 20, 2011

Evolution News & View is one of the main blogs for promoting Intelligent Design Creationism. Up 'till now it has not allowed comments but that has changed. Here's the new policy ...

Of course, you might want to discuss it with the scientists and scholars themselves. To that end, comments will be allowed on selected articles. All comments are held for moderation. The debate over evolution and intelligent design attracts all kinds, including those who detract from the conversation by their obnoxious behavior. In order to maintain a higher level of discourse, we will not publish comments that use foul language, ad hominem attacks, threats, or are otherwise uncivil.

By way of contrast, this blog and many others run by defenders of evolution will allow all comments except spam. We're not afraid of contrary opinions or uncivil behavior from creationists. We get them all the time.

One of Jerry Coyne's comments caught my eye because we've just been reading the Gould & Lewontin Spandrels paper in class. Coyne said,

Like the stories of the Bible, there’s no evolutionary psychology hypothesis that can be disconfirmed by data. If your story doesn’t hold up, simply concoct another story. Of course, there’s no evidence for the alternative stories, either.

In 1979 Gould and Lewontin wrote,

The admission of alternatives in principle does not imply their serious consideration in daily practice. We all say that not everything is adaptive; yet, faced with an organism, we tend to break it into parts and tell adaptive stories as if trade-offs among competing, well designed parts were the only constraint upon perfection for each trait. It is an old habit. As Romanes complained about A.R. Wallace in 1900: "Mr. Wallace does not expressly maintain the abstract impossibility of laws and causes other than those of utility and natural selection... Nevertheless, as he nowhere recognizes any other law or cause... he practically concludes that, on inductive or empirical grounds, there is no such other law or cause to be entertained. The adaptationist programme can be traced through common styles of argument. We illustrate just a few; we trust they will be recognized by all:

(1) If one adaptive argument fails, try another. Zig-zag commissures of clams and brachiopods, once widely regarded as devices for strengthening the shell, become sieves for restricting particles above a given size (Rudwick, 1964). A suite of external structures (horns, antlers, tusks) once viewed as weapons against predators, become symbols of intra-specific competition among males (Davitashvili, 1961). The eskimo face, once depicted as "cold engineered" (Coon, et al., 1950), becomes an adaptation to generate and withstand large masticatory forces (Shea, 1977). We do not attack these newer interpretations; they may all be right. We do wonder, though, whether the failure of one adaptive explanation should always simply inspire a search for another of the same general form, rather than a consideration of alternatives to the proposition that each part is "for" some specific purpose.

Wednesday, January 19, 2011

Science has published the Science Hall of Fame, a list of the most famous scientists of the past few hundred years. They compiled the list by counting the number of times that a scientist was mentioned in books published since 1800. The standard is Charles Darwin whose citations are set at 1000 milliDarwins. The only one who ranked higher was Bertrand Russell at 1500 milliDarwins.

Here are the top 25. The ones on the bottom have scores of 152. One remarkable thing about this list is how few of them are really famous for doing science. Many of them are cited in popular books for other reasons. Another remarkable thing about the list is that all of the scientists in the top 25 are dead.

The website has an interactive table that links you to Wikipedia articles. If you click on "Karl Pearson," for example, you'll learn about his science. You can also click on the citation score to see how their citations vary over time. I've copied the charts for Dawkins and Gould so you can see how they compare.

Monday, January 17, 2011

Check out the Marketplace show. If you live in Canada, go to Cure or Con?, otherwise watch it on YouTube (below). Our Center for Inquiry friends in Vancouver overdose at the beginning of the show. Will they survive?

Erica Johnson investigates one of the fastest growing alternative health treatments in the country: homeopathy. Ontario homeopaths are about to become the first province in Canada to regulate homeopathy — lending credibility to this unproven practice.

Canada's leading consumer ally takes a long hard look at the theories, and the remedies. For the first time in Canada, we conduct a test of homeopathic medicines, investigating the science behind these so-called medicines. In light of our results, we ask both the Ontario government and Health Canada why they are lending credibility to the homeopathic industry. Johnson also meets up with a rep from the world's leading manufacturer of homeopathic medicines, who admits that even the company doesn't know how homeopathy is supposed to work.

Watch, as we witness a Vancouver group of skeptics taking part in a group overdose of homeopathic remedies. Perhaps most disturbing we learn that some homeopaths are treating cancer patients with homeopathic remedies — this despite a leading cancer specialist saying there is no role for homeopathy in the treatment of cancer, that it is a "scam that is not evidence-based".

There are many well-known examples of alternative splicing. These examples have been taught in undergraduate courses for 30 years and they are prominently featured in textbooks. Alternative splicing exists.

Here's the problem. The explosion of EST data in the 1990's resulted in detection of many sequences suggesting that alternative splicing was much more widespread that previously suspected. The vast majority of these claims have not been verified and many of them have been removed from the annotated genomes published in the past few years.

Now we have a whole new set of claims based on high throughput analysis of transcripts from a variety of organisms and tissues. Many workers believe that the majority of human genes are alternatively spliced and some even publish articles stating that 95% of humans genes exhibit alternative splicing. One of my colleagues who makes such a claim says that just because a gene is alternatively spliced doesn't mean that the various isoforms of RNA are functional but I think that's disingenuous. If it's going to be a meaningful term then "alternative splicing" has to imply that that at least two different versions of RNA have some biological function.

I've asked repeatedly for evidence that some particular genes are alternatively spliced to give rise to two or more functional products. It should be possible to get this information from the databases used by these researchers—the ones that support their claim of widespread alternative splicing. Unfortunately, this has proven to be difficult. Whenever I search common alternative splicing databases I'm told that those databases aren't very good and the results aren't reliable.

Here's the challenge to all researchers who believe that a majority of human genes are alternatively spliced (in a biologically relevant manner). Show me your data. Pick one of the following sets of genes and demonstrate that most of them have functional alternatively spliced transcripts. If none of the genes in the set qualifies then explain why you reject the presumed alternative transcripts shown in popular databases. This shouldn't be much of a challenge if your claim is correct.

Note that this is a two part challenge. You have to first present evidence that there are functional alternative splicing events and then you also have to present the reasons why you reject some of the data from sequenced RNAs.

Here's an example from the human gene for triose phosphate isomerase (TPI1). The Entrez Gene entry is Gene ID: 7167. The primary entry shows one alternatively spliced transcript that removes the N-terminal coding region of the protein and creates an new larger N-terminal sequence. What is the evidence that this is biologically relevant? Now check out the known transcripts that have been detected according to UCSC Genome Browser, AceView, and Model Maker. These show additional variants affecting the splice junction sequences around exons 2, 4, and 6. Are these also examples of alternative splicing? Are they functional? If you reject these variants then what's the rationale for accepting some possible transcripts as real but rejecting others? Are some of them artifacts?

I selected these examples because we know the structures of the proteins so we can evaluate the possibility that an alternatively spliced message might produce a novel polypeptide chain. Of course there might be other reasons (regulation?) for producing alternatively spliced transcripts. Feel free to present the evidence.

Now it's possible that I've accidentally chosen sets of genes that do not exhibit alternative splicing. If that's the case then pick any other set of genes with a common function where the structure of the protein product is known. Meanwhile, you can explain why you reject all the putative splice variants for these genes.

Tuesday, January 11, 2011

Everyone interested in evolution should read the famous critique of the adaptationist program by Stephen Jay Gould (1941-2002) and Richard Lewontin (1929 - ). Whether you agree with them or not, it's essential that you become informed about the adpatationist-pluralist controversy—also known as the neutral-selectionist controversy. That controversy is still very much a part of the debates over evolution, although the adaptationist side tends to argue that the controversy has been settled.

It's no secret that I'm a huge fan of Gould and if I had my druthers I'd make students read every one of his books, including, The Structure of Evolutionary Theory. I'm a pluralist.

My friend John Wilkins, a philosopher, visited St. Mark's Square and the Basilica last year. He's on the opposite side of this debate and he offers the best defense of adaptationism that I've seen in recent years. You should keep an eye on his blog, Evolving Thoughts, it's a must-read for anyone who's serious about evolution. I blogged about John's version of adaptationism [An Adaptationist in Piazza San Marco].

This is a rich topic for undergraduates and there are many potential essay topics.

Gould, S.J. and Lewontin, R.C. (1979) The Spandrels of San Marco and the Panglossian Paradigm: A Critique of the Adaptationist Programme. Proceedings of the Royal Society of London. Series B, Biological Sciences, Vol. 205, No. 1161, The Evolution of Adaptation by Natural Selection (Sep. 21, 1979), pp. 581-598. [AAAS reprint] [printable version]

Today is the first day of my course on molecular evolution and I want the students to experience the give-and-take of scientific—and not so scientific—debate in the blogosphere.

Their first assignment is to read the following quotation from an article by Paul Davies and answer the question that follows.

Paul Davies is a professor at Arizona State University. He was trained as a physicist and he lists his interests as cosmology, quantum field theory, and astrobiology. The quotation is from an article he wrote last April in the Wall Street Journal [Is Anybody Out There?: After 50 years, astronomers haven't found any signs of intelligent life beyond Earth. They could be looking in the wrong places.]

Another physical object with enormous longevity is DNA. Our bodies contain some genes that have remained little changed in 100 million years. An alien expedition to Earth might have used biotechnology to assist with mineral processing, agriculture or environmental projects. If they modified the genomes of some terrestrial organisms for this purpose, or created their own micro-organisms from scratch, the legacy of this tampering might endure to this day, hidden in the biological record.

Which leads to an even more radical proposal. Life on Earth stores genetic information in DNA. A lot of DNA seems to be junk, however. If aliens, or their robotic surrogates, long ago wanted to leave us a message, they need not have used radio waves. They could have uploaded the data into the junk DNA of terrestrial organisms. It would be the modern equivalent of a message in a bottle, with the message being encoded digitally in nucleic acid and the bottle being a living, replicating cell. (It is possible—scientists today have successfully implanted messages of as many as 100 words into the genome of bacteria.) A systematic search for gerrymandered genomes would be relatively cheap and simple. Incredibly, a handful of (unsuccessful) computer searches have already been made for the tell-tale signs of an alien greeting.

Here's the question. Assume that the aliens inserted a 1000 bp message in the same place in the genomes of every member of our ancestral population from five million years ago. At that point every organism in the species had exactly the same message in a region of junk DNA.

If you were to sequence that very same region of your own genome what would the message look like today? Would it be different from the original message of five million years ago? Is there a way of reconstructing the original message and interpreting it?

Comments will be held until tomorrow evening in order to give everyone a fair shot at coming up with an answer.

Monday, January 10, 2011

Richard Feynman (1918–1988) was a very smart American physicist who's words are often quoted ... for good reason.

Here's one quotation where he describes how good scientists should behave. It's a point I make in my class on scientific controversies and it's worth emphasizing because so many modern scientists ignore it.

Feynman is specifically referrring to "cargo cult science" but his advice applies to a lot of of modern biology as well.

There is one feature I notice that is generally missing in "cargo cult science." It's a kind of scientific integrity, a principle of scientific thought that corresponds to a kind of utter honesty — a kind of leaning over backwards. For example, if you're doing an experiment, you should report everything that you think might make it invalid — not only what you think is right about it; other causes that could possibly explain your results; and things you thought of that you've eliminated by some other experiment, and how they worked — to make sure the other fellow can tell they have been eliminated.

Details that could throw doubt on your interpretation must be given, if you know them. You must do the best you can — if you know anything at all wrong, or possibly wrong — to explain it. If you make a theory, for example, and advertise it, or put it out, then you must also put down all the facts that disagree with it, as well as those that agree with it. There is also a more subtle problem. When you have put a lot of ideas together to make an elaborate theory, you want to make sure, when explaining what it fits, that those things it fits are not just the things that gave you the idea for the theory; but that the finished theory makes something else come out right, in addition.

In summary, the idea is to try to give all of the information to help others to judge the value of your contribution; not just the information that leads to judgment in one particular direction or another.

Sunday, January 09, 2011

Alex Ling alerted me to an important paper in last month's issue of PLoS Genetics. Pickrell et al. (2010) looked at low abundance RNAs in order to determine how many transcripts showed evidence of possible splicing errors. They found a lot of "alternative" spliced transcripts where the new splice junction was not conserved in other species and was used rarely. They attribute this to splicing errors. Their calculation suggests that the splicing apparatus makes a mistake 0.7% of the time.

This has profound implication for the interpretation of alternative splicing data. If Pickerell et al. are correct—and they aren't the only ones to raise this issue—then claims about alternative splicing being a common phenomenon are wrong. At the very least, those claims are controversial and every time you see such a claim in the scientific literature it should be accompanied by a statement about possible artifacts due to splicing errors. If you don't see that mentioned in the paper then you know you aren't dealing with a real scientist.

Here's the abstract and the author summary ..

Abstract

While the majority of multiexonic human genes show some evidence of alternative splicing, it is unclear what fraction of observed splice forms is functionally relevant. In this study, we examine the extent of alternative splicing in human cells using deep RNA sequencing and de novo identification of splice junctions. We demonstrate the existence of a large class of low abundance isoforms, encompassing approximately 150,000 previously unannotated splice junctions in our data. Newly-identified splice sites show little evidence of evolutionary conservation, suggesting that the majority are due to erroneous splice site choice. We show that sequence motifs involved in the recognition of exons are enriched in the vicinity of unconserved splice sites. We estimate that the average intron has a splicing error rate of approximately 0.7% and show that introns in highly expressed genes are spliced more accurately, likely due to their shorter length. These results implicate noisy splicing as an important property of genome evolution.

Author Summary

Most human genes are split into pieces, such that the protein-coding parts (exons) are separated in the genome by large tracts of non-coding DNA (introns) that must be transcribed and spliced out to create a functional transcript. Variation in splicing reactions can create multiple transcripts from the same gene, yet the function for many of these alternative transcripts is unknown. In this study, we show that many of these transcripts are due to splicing errors which are not preserved over evolutionary time. We estimate that the error rate in the splicing of an intron is about 0.7% and demonstrate that there are two major types of splicing error: errors in the recognition of exons and errors in the precise choice of splice site. These results raise the possibility that variation in levels of alternative splicing across species may in part be to variation in splicing error rate.

Saturday, January 08, 2011

Sandra Porter of Discovering Biology in a Digital World has recently attended a talk by Chris Mason of Cornell University. According to Sandra, Chris Mason made the following claims based on his analysis of RNAs from various tissues (human? mammal?). [Next Generation Sequencing adds thousands of new genes]

A large fraction of the existing genome annotation is wrong.

We have far more than 30,000 genes, perhaps as many as 88,000.

About ten thousand genes use over 6 different sites for polyadenylation.

98% of all genes are alternatively spliced.

Several thousand genes are transcribed from the "anti-sense"strand.

Lots of genes don't code for proteins. In fact, most genes don't code for proteins.

I bet that every one of those claims is wrong.

There's a saying about extraordinary claims—they require extraordinary evidence. In this case, I'm pretty sure the "evidence" is the detection of low abundance transcripts using highly sensitive sequencing technology. Anyone who's ever learned about DNA binding proteins knows about non-specific binding and they know that spurious transcription is inevitable. In order to overthrow our view of the number of genes and how they behave, you will have to convince me that you've ruled out accidental spurious transcription (junk RNA).

I think it's somewhat disingenuous to be giving a talk where you claim we have 88,000 genes and 98% of them are alternatively spliced. (The term "alternative splicing" implies biological significance and not just splicing errors.)

In order to evaluate transcriptome data we need to know the abundance of the transcript. It's not sufficient to simply report that such-and-such region of the genome was transcribed. Researchers have got to report the average number of transcripts per cell in the tissue they are analyzing. I'm betting that if we saw that data we would instantly recognize that the so-called new "genes" are producing less than one transcript per cell. If that's the case it can't be biologically significant in a large mammalian cell.

Friday, January 07, 2011

When it comes to comparing DNA sequences of individual genes, the human and chimp versions are almost identical in sequence. They differ by only 1-2%. That result gave rise to the oft-quoted similarity of 98-99%.

But that's not the whole story. Outside of the genes there's a large amount of DNA that's less similar. We know this because we now have the sequences of both the human and chimp genomes. Furthermore, there are sequences present in the human genome that are absent in the chimp genome and vice versa. If you look at the whole genomes, the overall similarity is about 95% or so depending on how you do the calculation.

Creationists make a big deal about this. They claim that the newest data proves that evolutionists are wrong and chimps aren't necessarily our cousins. The latest debate is between Fazale Rana on the Reasons to Believe (RTB) website and Dennis Venema on the BioLogos website. The important scientific point is about the actual similarity and how is it calculated?

Fortunately for us, Todd Wood of the Center for Origins Research at Bryan College in Dayton, Tennessee, USA is on the case. Todd belongs to a young-Earth creation study group [BSG] but don't let that fool you. He's doing a pretty good job of sorting out the facts in the case.

Conor Cunningham1 has just published a defense of Christianity against the attack of Darwinism. I've ordered his book, Darwin's Pious Idea: Why the Ultra-Darwinists and Creationists Both Get it Wrong, and I look forward to commenting on it in future posts.

Meanwhile, here's an excerpt from his BBC series Did Darwin Kill God? You can see right away that there's going to be problem with someone who equates Darwin with modern evolutionary theory. It means that Cunningham lacks scientific credibility making his arguments mostly moot.

There might be a problem with his theology as well but that's not something I'm very interested in. Perhaps some theist can answer a question? If Genesis has always been taken metaphorically and not literally by the Christian church, then what about the rest of the Bible? Specifically, are Christian supposed to take the stories of Jesus as metaphor and not fact? Is the death and resurrection of Jesus something that never actually happened? Is it just a metaphor? What the official Christian view of this?

Conor Cunningham is a lecturer in theology and religious studies at the University of Nottingham in the United Kingdom.

Laurence A. Moran

Larry Moran is a Professor in the Department of Biochemistry at the University of Toronto. You can contact him by looking up his email address on the University of Toronto website.

Sandwalk

The Sandwalk is the path behind the home of Charles Darwin where he used to walk every day, thinking about science. You can see the path in the woods in the upper left-hand corner of this image.

Disclaimer

Some readers of this blog may be under the impression that my personal opinions represent the official position of Canada, the Province of Ontario, the City of Toronto, the University of Toronto, the Faculty of Medicine, or the Department of Biochemistry. All of these institutions, plus every single one of my colleagues, students, friends, and relatives, want you to know that I do not speak for them. You should also know that they don't speak for me.

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Quotations

The old argument of design in nature, as given by Paley, which formerly seemed to me to be so conclusive, fails, now that the law of natural selection has been discovered. We can no longer argue that, for instance, the beautiful hinge of a bivalve shell must have been made by an intelligent being, like the hinge of a door by man. There seems to be no more design in the variability of organic beings and in the action of natural selection, than in the course which the wind blows.Charles Darwin (c1880)Although I am fully convinced of the truth of the views given in this volume, I by no means expect to convince experienced naturalists whose minds are stocked with a multitude of facts all viewed, during a long course of years, from a point of view directly opposite to mine. It is so easy to hide our ignorance under such expressions as "plan of creation," "unity of design," etc., and to think that we give an explanation when we only restate a fact. Any one whose disposition leads him to attach more weight to unexplained difficulties than to the explanation of a certain number of facts will certainly reject the theory.

Charles Darwin (1859)Science reveals where religion conceals. Where religion purports to explain, it actually resorts to tautology. To assert that "God did it" is no more than an admission of ignorance dressed deceitfully as an explanation...

Quotations

The world is not inhabited exclusively by fools, and when a subject arouses intense interest, as this one has, something other than semantics is usually at stake.
Stephen Jay Gould (1982)
I have championed contingency, and will continue to do so, because its large realm and legitimate claims have been so poorly attended by evolutionary scientists who cannot discern the beat of this different drummer while their brains and ears remain tuned to only the sounds of general theory.
Stephen Jay Gould (2002) p.1339
The essence of Darwinism lies in its claim that natural selection creates the fit. Variation is ubiquitous and random in direction. It supplies raw material only. Natural selection directs the course of evolutionary change.
Stephen Jay Gould (1977)
Rudyard Kipling asked how the leopard got its spots, the rhino its wrinkled skin. He called his answers "just-so stories." When evolutionists try to explain form and behavior, they also tell just-so stories—and the agent is natural selection. Virtuosity in invention replaces testability as the criterion for acceptance.
Stephen Jay Gould (1980)
Since 'change of gene frequencies in populations' is the 'official' definition of evolution, randomness has transgressed Darwin's border and asserted itself as an agent of evolutionary change.
Stephen Jay Gould (1983) p.335
The first commandment for all versions of NOMA might be summarized by stating: "Thou shalt not mix the magisteria by claiming that God directly ordains important events in the history of nature by special interference knowable only through revelation and not accessible to science." In common parlance, we refer to such special interference as "miracle"—operationally defined as a unique and temporary suspension of natural law to reorder the facts of nature by divine fiat.
Stephen Jay Gould (1999) p.84

Quotations

My own view is that conclusions about the evolution of human behavior should be based on research at least as rigorous as that used in studying nonhuman animals. And if you read the animal behavior journals, you'll see that this requirement sets the bar pretty high, so that many assertions about evolutionary psychology sink without a trace.

Jerry Coyne
Why Evolution Is TrueI once made the remark that two things disappeared in 1990: one was communism, the other was biochemistry and that only one of them should be allowed to come back.

Sydney Brenner
TIBS Dec. 2000
It is naïve to think that if a species' environment changes the species must adapt or else become extinct.... Just as a changed environment need not set in motion selection for new adaptations, new adaptations may evolve in an unchanging environment if new mutations arise that are superior to any pre-existing variations

Douglas Futuyma
One of the most frightening things in the Western world, and in this country in particular, is the number of people who believe in things that are scientifically false. If someone tells me that the earth is less than 10,000 years old, in my opinion he should see a psychiatrist.

Francis Crick
There will be no difficulty in computers being adapted to biology. There will be luddites. But they will be buried.

Sydney Brenner
An atheist before Darwin could have said, following Hume: 'I have no explanation for complex biological design. All I know is that God isn't a good explanation, so we must wait and hope that somebody comes up with a better one.' I can't help feeling that such a position, though logically sound, would have left one feeling pretty unsatisfied, and that although atheism might have been logically tenable before Darwin, Darwin made it possible to be an intellectually fulfilled atheist

Richard Dawkins
Another curious aspect of the theory of evolution is that everybody thinks he understand it. I mean philosophers, social scientists, and so on. While in fact very few people understand it, actually as it stands, even as it stood when Darwin expressed it, and even less as we now may be able to understand it in biology.

Jacques Monod
The false view of evolution as a process of global optimizing has been applied literally by engineers who, taken in by a mistaken metaphor, have attempted to find globally optimal solutions to design problems by writing programs that model evolution by natural selection.